A number of agents are well known to reduce elevated levels of LDL and cholesterol, for example hypocholesterolaemic agents such as clofibrate, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors such as simvastatin and fluvastatin as well as agents which act by complexing with bile acids in the intestinal system. Illustrative of such latter agents is that known as cholestyramine described, inter alia, in UK patent Ser. No. 929,391 and which is a cross-linked polystyrene resin in which a proportion of the styrene units bear an ionic trimethylammonium group. It is believed that many of such agents act by sequestering bile acids within the intestinal tract, thus lowering levels of bile acid circulating in the enterohepatic system and promoting replacement of bile acids by synthesis in the liver from cholesterol, which synthesis results, inter alia, in a lowering of circulating blood cholesterol levels. The use of bile acid sequestering agents such as cholestyramine and colestipol in treating conditions such as familial hypercholesterolaemia is known, as is their use in preventing or limiting the progression of diseases such as coronary heart disease associated with high levels of blood lipids such as cholesterol, and in alleviating adverse conditions affecting the intestinal tract such as diarrhea. However, there is a continuing need for new alternative agents, in particular because many of the existing agents are not particularly potent and produce adverse side-effects. Thus, it is frequently necessary to administer comparatively large amounts (up to 25 g daily) of presently available polymeric agents, such as cholestyramine and colestipol, to produce a beneficial effect. Patient compliance with dosing regimes involving such large amounts of relatively unpalatable polymeric agents is difficult to achieve.
Insoluble poly(allylamine) polymeric materials have been known for some time, for example as described in European patent application, publication no. 143,328 pending. However, they have not previously been known to be of value as pharmaceutical agents. We have now discovered, and this is a basis for our invention, that a series of novel, polymeric allylamine derivatives containing quaternary ammonium groups possess useful activity in reducing plasma sterol levels (for example, cholesterol levels) at relatively low doses and with a reduced propensity towards the production of significant side-effects.